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Use of genetically modified bacteria for drug delivery in humans: Revisiting the safety aspect

The use of live, genetically modified bacteria as delivery vehicles for biologics is of considerable interest scientifically and has attracted significant commercial investment. We have pioneered the use of the commensal gut bacterium Bacteroides ovatus for the oral delivery of therapeutics to the g...

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Detalles Bibliográficos
Autores principales: Wegmann, Udo, Carvalho, Ana Lucia, Stocks, Martin, Carding, Simon R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5442108/
https://www.ncbi.nlm.nih.gov/pubmed/28536456
http://dx.doi.org/10.1038/s41598-017-02591-6
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author Wegmann, Udo
Carvalho, Ana Lucia
Stocks, Martin
Carding, Simon R.
author_facet Wegmann, Udo
Carvalho, Ana Lucia
Stocks, Martin
Carding, Simon R.
author_sort Wegmann, Udo
collection PubMed
description The use of live, genetically modified bacteria as delivery vehicles for biologics is of considerable interest scientifically and has attracted significant commercial investment. We have pioneered the use of the commensal gut bacterium Bacteroides ovatus for the oral delivery of therapeutics to the gastrointestinal tract. Here we report on our investigations of the biological safety of engineered B. ovatus bacteria that includes the use of thymineless death as a containment strategy and the potential for the spread of transgenes in vivo in the mammalian gastrointestinal tract. We demonstrate the ability of GM-strains of Bacteroides to survive thymine starvation and overcome it through the exchange of genetic material. We also provide evidence for horizontal gene transfer in the mammalian gastrointestinal tract resulting in transgene-carrying wild type bacteria. These findings sound a strong note of caution on the employment of live genetically modified bacteria for the delivery of biologics.
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spelling pubmed-54421082017-05-25 Use of genetically modified bacteria for drug delivery in humans: Revisiting the safety aspect Wegmann, Udo Carvalho, Ana Lucia Stocks, Martin Carding, Simon R. Sci Rep Article The use of live, genetically modified bacteria as delivery vehicles for biologics is of considerable interest scientifically and has attracted significant commercial investment. We have pioneered the use of the commensal gut bacterium Bacteroides ovatus for the oral delivery of therapeutics to the gastrointestinal tract. Here we report on our investigations of the biological safety of engineered B. ovatus bacteria that includes the use of thymineless death as a containment strategy and the potential for the spread of transgenes in vivo in the mammalian gastrointestinal tract. We demonstrate the ability of GM-strains of Bacteroides to survive thymine starvation and overcome it through the exchange of genetic material. We also provide evidence for horizontal gene transfer in the mammalian gastrointestinal tract resulting in transgene-carrying wild type bacteria. These findings sound a strong note of caution on the employment of live genetically modified bacteria for the delivery of biologics. Nature Publishing Group UK 2017-05-23 /pmc/articles/PMC5442108/ /pubmed/28536456 http://dx.doi.org/10.1038/s41598-017-02591-6 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Wegmann, Udo
Carvalho, Ana Lucia
Stocks, Martin
Carding, Simon R.
Use of genetically modified bacteria for drug delivery in humans: Revisiting the safety aspect
title Use of genetically modified bacteria for drug delivery in humans: Revisiting the safety aspect
title_full Use of genetically modified bacteria for drug delivery in humans: Revisiting the safety aspect
title_fullStr Use of genetically modified bacteria for drug delivery in humans: Revisiting the safety aspect
title_full_unstemmed Use of genetically modified bacteria for drug delivery in humans: Revisiting the safety aspect
title_short Use of genetically modified bacteria for drug delivery in humans: Revisiting the safety aspect
title_sort use of genetically modified bacteria for drug delivery in humans: revisiting the safety aspect
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5442108/
https://www.ncbi.nlm.nih.gov/pubmed/28536456
http://dx.doi.org/10.1038/s41598-017-02591-6
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